Using the rat hypothalamo-neurohypophysial system as a model, we have isolated two large molecular weight common precursors, one for oxytocin and its neurophysin (Prooxyphysin), and the other for vasopressin and its neurophysin (Propressophysin). Propressophysin has a mw = 19,500 (pI=6.1) and is a glycopeptide. Prooxyphysin has a mw = 15,000 (pI=5.4) and lacks the glycopeptide component. The glycopeptide from propressophysin has been isolated, its amino acid composition and the first 20 amino acids of its sequence have been determined. We have also demonstrated that the two prohormones are present in secretory granules, and their processing to the respective hormones can occur intragranularly.